Nanoparticles can improve the positive rate of metastatic lymph node in thyroid cancer surgery

To investigate the application of carbon nanoparticles in lymph node dissection and parathyroid gland protection during thyroid cancer surgery. Retrospective analysis was performed on 282 cases of thyroid cancer surgery in our hospital from 2018 to 2019. All patients underwent total thyroidectomy and cervical central lymph node dissection. Nanocarbon was not used in the control group, but was used in the experimental group. The general situation of the patients, the number of postoperative lymph nodes and the number of metastasis were collected, and the differences between serum parathyroid hormone and blood calcium were compared before and on the 3rd and 30th day after surgery.


Conclusion.
The application of carbon nanoparticles in thyroid cancer surgery can signi cantly increase the number of lymph nodes seized and the positive rate of metastatic lymph node removal, but the protection of parathyroid gland is not obvious.

Background
Thyroid cancer is the most common endocrine malignant tumor, and the most common pathological type is papillary thyroid cancer (PTC), accounting for more than 90% of the total thyroid cancer 1-2 .Surgical treatment is the main treatment of this disease 3 ,because of its high rate of lymph node metastasis 4] therefore, the routine cervical lymph node dissection in China increases the injury rate of parathyroid gland and the risk of postoperative hypocalcaemia with the expansion of surgical scope 5 .Studies have shown that carbon nanoparticles can darken lymph nodes and negatively develop parathyroid glands 6 ,it is widely used in thyroid surgery, but whether carbon nanoparticles have a protective effect on parathyroid glands is controversial 10,17 .The purpose of this study was to investigate the value of carbon nanoparticles in thyroid cancer surgery and cervical central lymph node dissection. Subjects And Methods

Case data
This study is a retrospective analysis of relevant case data from the rst a liated hospital of Jinzhou Medical University, and does not involve ethical issues.The clinical data of 282 patients who underwent surgical treatment for thyroid cancer in our department from January 2018 to June 2019 were retrospectively analyzed. Inclusion criteria were :(1) all patients underwent total thyroidectomy and underwent unilateral or bilateral cervical central lymph node dissection (2) all patients had no distant metastasis. (3) thyroid papillary carcinoma was con rmed pathologically (4) thyroid surgery was performed for the rst time (5) preoperative imaging showed no lymph node metastasis in the cervical region (6)preoperative PTH and blood calcium measurements were within the normal range. Exclusion

surgical methods
All patients underwent total thyroidectomy and cervical central lymph node dissection. The thyroid gland was routinely exposed. In the experimental group, 0.1ml of carbon nanoparticles was injected into the affected side at 1-2 points through a 1ml syringe. After that, the injection point was pressed with gauze to prevent nano-carbon leakage. After 10min, the lymph nodes were blackened and then the adenoidectomy was performed. During the operation, the thyroid papillary carcinoma was con rmed by rapid freezing pathology. Intraoperative attention was paid to ne dissection of thyroid capsule. The number of lymph nodes removed and the number of metastatic lymph nodes were compared between the two groups.

statistical analysis
The collected clinical data were statistically analyzed by SPSS 22 software. The counting data were expressed as a percentage (%), and 2 test were performed. The measurement data is expressed by t test. P < 0.05 was considered statistically signi cant.

comparison of basic conditions between the two groups
There was no signi cant difference in age, gender, tumor size and TNM stage between the experimental group (162 cases) and the control group (120 cases) (P >.05), as shown in table 1.

Lymph node detection
The total number of lymph nodes detected in the experimental group was 1587, compared with 810 in the control group, the difference was statistically signi cant (P < 0.05). The detection of metastatic lymph nodes in the experimental group was signi cantly different from that in the control group (P < 0.05). See table 2 for details.

Postoperative changes in serum calcium and PTH
There was no signi cant difference in serum calcium and PTH levels between the two groups before and after 3 and 30 days, as shown in table 3.

Discuss
Papillary carcinoma of the thyroid (PTC) is the most common thyroid malignancy, with lymph node metastasis rates reported to be as high as 50-70% in patients with PTC 7 , However, incomplete intraoperative lymph node dissection is an important factor causing postoperative recurrence in patients, and expanding the scope of dissection will increase the risk of damage to the parathyroid gland. The position of the superior parathyroid gland is relatively xed, while the position of the inferior parathyroid gland varies greatly 8 ,Multiple lymph node metastases often require extensive dissection, which may damage the parathyroid gland or even cut it by mistake, seriously affect the prognosis and quality of life of patients, and even threaten the life of patients. Therefore, how to protect the parathyroid gland while removing lymph nodes is the key.
Carbon nanoparticles with an average diameter of 150nm can enter lymphatic vessels (with an average diameter of 500nm) rather than capillaries (with an average diameter of 30-50nm), allowing the development of lymph nodes. Since the lymphatic vessels of thyroid gland and parathyroid gland do not communicate with each other, most scholars believe that negative development of parathyroid gland has a protective effect on it, and it has been widely used in thyroid cancer surgery in recent years 9 .The results of this study showed that there was a signi cant statistical difference between the experimental group and the control group in the total number of lymph nodes cleared and the positive rate of metastatic lymph nodes. Consistent with the views of luo wenzheng and other researchers [10][11][12] 11111111111156456466---][i]222115415,Considering carbon nanoparticles can help surgeons better identify lymph nodes in the central region, especially the microscopic nodes that are di cult to be distinguished by the naked eye, reduce lymph node residues, and make it easier and more accurate for pathologists to extract lymph nodes 13 .Together, the two can increase the number of lymph nodes detected, and the corresponding seizure rate of metastatic lymph nodes is also improved, which is conducive to more accurate postoperative judgment of staging and prognosis, as well as elimination of potential sources of lymph node recurrence [14][15] .However, there was no statistical difference in the changes of blood calcium and PTH between the experimental group and the control group at 3 and 30 days after surgery (P > 0. 05), which was consistent with the views of Liu et al [16][17] ] that is, the parathyroid protection is not signi cant. We think it may be caused by the following reasons: The recognition of parathyroid gland is closely related to the surgical experience of surgeons. Experienced physicians can completely identify the parathyroid gland by the color, texture and appearance of the parathyroid gland with the naked eye, without other development techniques to protect the parathyroid gland. In some cases, intraoperative leakage may occur due to improper handling of nanocarbons. In this case, the wound may be contaminated, making it impossible for the accessory glands to identify the nanocarbons and causing accidental injury. For small glands the dose of carbon nanoparticles should be reduced.
In conclusion, although nanocarbon does not signi cantly protect the parathyroid gland, it can signi cantly improve the number of seized lymph nodes and the positive rate of metastatic lymph node removal, facilitate accurate postoperative judgment of the stage and prognosis of patients, and reduce the recurrence rate. Therefore, nanocarbon is worth promoting for young doctors and doctors in primary hospitals. The sample size included in this study is relatively small, and there is a lack of research on longer follow-up and survival analysis of patients, so more in-depth research is needed to explore its use value.

Conclusion
We found that the application of carbon nanoparticles in thyroid cancer surgery can signi cantly increase the number of detected lymph nodes and the positive rate of metastatic lymph node clearance, but the protection of parathyroid gland is not obvious. A larger sample study may be needed.  Tables   Table 1 basic situation analysis table of